Assessment of dopaminergic pathways in Huntington’s Disease: when, how, why? A (clinician-friendly) systematic review of the literature on PET and SPECT applications

Purpose: Positron Emission Tomography (PET) and Single Photon Emission Computerized Tomography (SPECT) allow the in-vivo evaluation of brain dopaminergic pathways’ integrity and functionality. A systematic review of published literature was performed to determine the usefulness of PET and SPECT for the assessment of dopaminergic pathways in patients with Huntington’s Disease (HD). Methods: PubMed/Medline databases were searched to identify studies responding to our aim. Included articles were appraised using the Quality Assessment of Diagnostic Accuracy Studies criteria. Evaluation and discussion of data was then designed to assist clinicians identifying when (during patients’ course of the disease), how (through PET or SPECT) and why (depending on the findings) it would be useful to perform a functional assessment of dopaminergic pathways in patients with manifest and pre-manifest HD. Results: Of 572 articles found, 33 were included in this systematic review, 6 among which evaluated the application of SPECT, and 27 the application of PET. Overall, there was an agreement in reporting dopaminergic system degeneration at both striatal and extra-striatal levels, often correlated with clinical and neuropsychological parameters. The non-linear progressive reduction of presynaptic dopamine transporter, vesicular monoamine transporter-2, or of post-synaptic dopamine receptors D1 and D2 was constantly described having a high potential of offering sensitive biomarkers of disease progression and response to disease-modifying interventions. Conclusions: Despite limited literature data, this systematic review revealed that SPECT and PET are useful to monitor different aspects of striatal and extra-striatal dopaminergic pathways degeneration during all stages of HD and may serve for response to disease-modifying interventions assessment.